The present invention is concerned with certain 2,6-substituted pyridines, their preparation and use as herbicides.
Pyridines and pyridine derivatives have many uses, for example, as pharmaceuticals, pesticides (herbicides, acaricides, anthelmintics, and bird repellants), feed supplements, solvents, reagents, intermediates, and chemicals for the polymer and textile industry. Various 2,6-diaryloxy- or -diarylmethoxy-pyridine derivatives have been investigated for such uses, the compounds often having additional substitution of the central pyridine ring.
European Patent A2-180188 is concerned with 2-hydroxy-pyridine derivatives, for example 2,6-dihydroxypyridines, as potentiators for increasing the anticancer activity of 5-fluorouracil and related compounds. The preparation and debenzylation of 2,6-dibenzyloxy-3-chloropyridine is disclosed. In J. Biol. Chem., 72, Vol. 247(23), pages 7628 to 7633, (which is concerned with the synthesis of 2,3,6-trihydroxypyridine and accumulation and partial characteristics of the product of 2,6-dihydroxypyridine oxidation) the Grignard reaction of 3-bromo-2,6-dibenzyloxypyridine with isopropyl bromide is disclosed. There is no disclosure of biological activity for 2,6-dibenzyloxy-3-chloropyridine nor its bromo analogue.
2,6-di(3-methylphenoxy)-pyridine is disclosed in French Patent Specification No. 1527714 which is concerned with polyethers containing a 2,6-linked pyridine group. U.S. Pat. No. 4,830,846 is concerned with a separation process for anhydrous HCl and HBr by thermal cleavage utilizing a hindered pyridine, one example of which being 2,6-diphenoxypyridine. Again no biological activity is disclosed for these aryloxy pyridines.
The dibenzyloxy analogue of 2,6-diphenoxypyridine in addition to being mentioned in JP-A-63250324, EP-A-180188 and J. Med. Chem. 10(2), pages 320 to 325, all medical research publications, was prepared as an example of the herbicidal compounds proposed in U.S. Pat. No. 3,535,328 and the divisional published as U.S. Pat. No. 3,687,959. Both texts are predominantly directed to the herbicidal, fungicidal, and, for the compounds claimed in U.S. Pat. No. 3,535,328, nematocidal and insecticidal activity, of amido or aminothioethoxy derivatives. No herbicidal activity data is given for the disclosed 2,6-dibenzyloxypyridine.
Herbicidal evaluation of 2,6-dibenzyloxypyridine and its analogue 2,6-diphenoxypyridine now undertaken has revealed that the compounds have herbicidal activity primarily against representative broadleaf plant species in post-emergence foliar spray application but little or no post-emergence action against representative grass-type plants and a complete absence of pre-emergence herbicidal activity.
Surprisingly, it has now been found that certain substituted forms of 2,6-diphenoxypyridine and 2,6-dibenzloxypyridine, and also the related asymmetric 2-phenoxy-6-dibenzyloxy-pyridines, have a significantly different spectrum of activity and not only possess high activity against broadleaf plants in foliar spray applications but also have significant action against grass-type plants, particularly against the important weed, barnyard grass; a number of examples additionally being effective against both plant types pre-emergence.
Accordingly, the present invention provides a herbicidal composition which comprises a carrier and, as an active ingredient, a compound of the general formula ##STR2## in which each of n and m independently is 0 or 1; each of Ar.sup.1 and Ar.sup.2 independently is aryl, at least one of Ar.sup.1 and Ar.sup.2 being substituted by one or more of the substituents selected from halogen, alkyl, alkoxy, haloalkyl and haloalkoxy; and R.sup.1 is a hydrogen atom, or alkyl, alkylthio or haloalkyl having from 1 to 4 carbon atoms, and R.sup.2 is hydrogen or halogen provided that at least one of R.sup.1 and R.sup.2 is hydrogen.
An alkyl group, unless otherwise specified may be a straight chain or branched chain group suitably containing up to 12 carbon atoms, preferably from 1 to 4 carbon atoms. An alkyl portion of a haloalkyl, alkylthio, alkoxy or haloalkoxy group suitably has from 1 to 4 atoms, preferably 1 or 2 carbon atoms.
Halogen is fluorine, chlorine, bromine or iodine. Haloalkyl and haloalkoxy are preferably mono-, di- or tri-fluoroalkyl and -alkoxy, especially trifluoromethyl and trifluoromethoxy.
An aryl group is preferably a phenyl group.
The Ar.sup.1 --(CH.sub.2).sub.n --0-- and Ar.sup.2 --CH.sub.2).sub.m --0-- portions of compounds of formula I are identical or different. Thus the compounds are symmetrical or asymmetrical diaryloxypyridines or diarylmethoxy-pyridines, or are aryloxyarylmethoxypyridines.
Preferably one of n and m is 1 and the other is 0 or 1, but most preferably each of n and m is 1.
At least one of the groups Ar.sup.1 and Ar.sup.2 is substituted. Suitable substituents include methoxy and trifluoromethoxy groups and, preferably, methyl, flourine, chlorine, or trifluoromethyl. From 1 to 5 substituents are present; preferably 1 or 2 substituents.
R.sup.1 is preferably a hydrogen atom or a methyl, methylthio or trifluoromethyl group. Especially preferred is hydrogen or methyl.
R.sup.2 is suitably a hydrogen or chlorine atom, especially a hydrogen atom.
Preferred compounds fall in the following categories, with reference to the symbols used in general formula I:
(i) n is 0; m is 0; R.sup.1 and R.sup.2 each represents a hydrogen atom; Ar.sup.1 represents a trifluoromethylphenyl group, especially a 3-trifluoromethylphenyl group; and Ar.sup.2 represents an unsubstituted or chloro- or trifluoromethyl-substituted phenyl group; PA1 (ii) n is 0; m is 1; R.sup.1 and R.sup.2 each represents a hydrogen atom; Ar.sup.1 represents a substituted phenyl group, especially a 3-trifluoromethylphenyl group; and Ar.sup.2 represents an unsubstituted phenyl group or a fluoro-substituted phenyl group; PA1 (iii) n is 1; m is 1; R.sup.1 and R.sup.2 each represents a hydrogen atom; and each of Ar.sup.1 and Ar.sup.2 represents a fluoro- or methyl- substituted phenyl group, especially ortho and/or para substituted, e.g., 2- or 4- fluorophenyl group or a 2-methyl group. PA1 a) when n and m are 0, then both Ar.sup.1 and Ar.sup.2 are not 3-methylphenyl; and PA1 b) when n and m are both 1, then R.sup.2 does not represent a chlorine or bromine atom. PA1 a) to obtain a compound of formula I in which Ar.sup.1 and Ar.sup.2 are the same, reacting a metal salt of a compound of general formula EQU Ar.sup.1 (CH.sub.2).sub.n OH (II) PA1 in which Ar.sup.1 and n are as defined above, with a 2,6-halopyridine of the formula ##STR3## in which Hal.sup.1 and Hal.sup.2 each, independently, represent a halogen atom, and R.sup.1 and R.sup.2 are as defined above, in a molar ratio of at least 2:1 PA1 b) to obtain a compound of formula I in which Ar.sup.1 and Ar.sup.2 are different, reacting a compound of formula II with a 2,6-dihalopyridine of formula III in a molar ratio of 1:1 and then reacting the resulting product with a metal salt of a compound of the formula IV EQU Ar.sup.2 (CH.sub.2).sub.n OH (IV) PA1 in which Ar.sup.2 and n are as defined in claim 1, in a molar ratio of at least 1:1, each reaction stage being carried out in the presence of an organic solvent.
Most of the compounds of general formula I are novel and accordingly the present invention provides a compound of general formula I in which n, m, Ar.sup.1, Ar.sup.2, R.sup.1 and R.sup.2 have the meanings given above with the proviso that
The compounds of formula I may be prepared by appropriate adaptation of conventional methods of obtaining substituted pyridine compounds, the basic technique being, for example, reaction of a metal salt of the appropriate alcohol with an appropriate 2,6-dihalopyridine, in a solvent and suitably at elevated temperature, ideally at reflux. For symmetrical pyridine compounds preparation, the reaction can be carried out in one step by using a molar ratio of salt to pyridine of at least 2:1. For asymmetrical compounds of formula I, separate introduction of the two substituents is required in a two-stage process.
The present invention therefore provides a process for the preparation of a compound of formula I, which comprises
or
The metal salt of the alcohol of formula II is conveniently an alkali metal salt, for example a sodium or potassium salt, and is conveniently generated by reaction of the alcohol with a suitable metal base, for example a metal carbonate or hydride. Preferably the metal salt is a sodium salt generated using sodium hydride.
The organic solvent utilized in the reaction would be selected depending on the nature of the reactants involved. Generally any polar organic solvent is suitable, for example dimethylformamide and tetrahydrofuran.
Hal.sup.1 and Hal.sup.2 conveniently are both the same, each representing a chlorine or bromine atom.
The prepared compounds of formula I may, if desired, be isolated and purified using conventional techniques.
Compounds of general formula II, III and IV are generally known and/or are easily preparable by standard techniques.
The present invention also provides the use of a compound of formula I as a herbicide. Further, in accordance with the invention there is provided a method of combating undesired plant growth at a locus by treating the locus with a composition according to the invention or a compound of formula I. As the most useful action is by foliar spray application, the locus is most suitably the plants in a crop area, typical crops being cereals. However, application may also be to the soil for those compounds having pre-emergence herbicidal action. The dosage of active ingredient used is in the range of from about 0.01 kg/ha to about 10 kg/ha, preferably about 0.1 kg/ha to about 1.0 kg/ha.
While all compounds of the present invention have useful activity against broadleaf and narrowleaf plants, exceptionally good activity is shown by compounds in which at least one of n and m is 1, particularly in the phenoxy/benzyloxy pyridines and, most preferably, in the dibenzyloxypyridines of the present invention.
The present invention also extends to a method of making a herbicidal composition of the invention which comprises bringing a compound of formula I into association with at least one carrier.
Preferably, there are at least two carriers in a composition of the present invention, at least one of which carriers is a surface-active agent.
A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may be, as appropriate, a plant, seed or soil, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any of the carriers normally used in formulating herbicidal compositions may be used. Preferably compositions according to the invention contain about 0.5% to about 95% by weight of active ingredient.
Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; elements, for example carbon and sulphur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes; and solid fertilizers, for example superphosphates.
Suitable liquid carriers include water; alcohols, for example ispropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosine and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane. Mixtures of different liquids are often suitable.
Agricultural compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution. Thus preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which carriers is a surface-active agent.
A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters of glycerol, sorbitol, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaline earth metal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts of sulphonated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulphonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.
The herbicidal composition of the invention may also contain other active ingredients, for example compounds possession insecticidal or fungicidal properties, or other herbicides.